Background/Purpose:  Direct oral anticoagulants (DOACs) are approved for the treatment of venous, and prevention of venous/arterial thrombosis. There have been case reports/ series where DOACs have been used in antiphospholipid syndrome (APS) with controversial results. Our objective was to describe the clinical characteristics of and thrombosis risk in APS patients treated with DOACs.

Methods: A web-based data capture system stores patientsÕ clinical and laboratory characteristics in the context of the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository (ÔRegistryÕ), which has been created to study the natural course of persistently aPL-positive patients with/without autoimmune diseases (AIDx) over 10 years. The inclusion criteria are aPL positivity according to the Updated Sapporo Classification Criteria. For this descriptive study, we analyzed the demographics, clinical characteristics, and outcomes of aPL-positive patients who have been treated with DOACs.

Results: As of 4/2016, 627 aPL-positive patients were recruited (aPL/APS without any other AIDx: 410 [thrombotic APS with/without obstetric APS: 286]; and aPL/APS associated with another AIDx: 217 [thrombotic APS with/without obstetric APS: 142]).  Of 428 thrombotic APS patients, 19 (4.4%) were current or past DOAC users (rivaroxaban: 17; dabigatran: 2).Of 19 patients, 17 (90%) had history of thrombosis; however only seven [37%] had single venous thrombosis.  The indications for DOAC use were: INR lability (n:3); recurrent thrombosis or adverse events on warfarin (n: 4); first line therapy for thrombosis treatment (n:2) and prevention (n:2); clinical trial (n:5); and patientsÕ request (n: 3). The follow up time on DOACs was 1- 84m (mean ± SD: 23.3 ± 22.3m). Recurrent vascular events were reported in six patients (32%) (including 1 microthrombosis; 4 retrospective; and 2 prospective) (Table).  One of two patients with prospective follow-up had cardiovascular disease risk factors at the time of the event. The annual incident thrombosis risk was 16.2% (for comparison, the risk was 2.1% for warfarin-users).

Conclusion: Based on a descriptive analysis of a large-scale international aPL/APS registry, less than five percent of patients receive a DOAC, mostly rivaroxaban. One-third of these patients developed recurrent events during the two-year follow-up; however, in approximately 60% of these patients the DOAC use was not as per licensed indications aside from the APS diagnosis. Although the small number of patients and the retrospective/prospective nature of the data collection might have resulted in a relatively high recurrence rate, DOAC use in APS should be guided by the results of appropriate randomized clinical trials. Currently no recommendations can be made against or for the use of DOACs in APS.